Secretion of transmitters, hormones, and other biologically active molecules depends upon a complex sequence of cellular events. Although some cells like nerve and muscle cells can communicate through electrical signals, most cells communicate through chemical agents that alter the activity of the cells from which they are released (known as autocrine agents), nearby cells (paracrine agents or transmitters), or cells in other parts of the organism (exocrine agents or hormones). Normal cellular function usually depends upon the very tight control of the amount and timing of the release of these agents. Many pathological events involve disruption of chemical communication between cells (most notably in the central nervous system, heart, lungs, and kidneys). Because of the importance of these chemical messengers, an enormous research effort has been directed to determining the properties of release from cells. However, because most of these methods are indirect or have low spatial or temporal resolution, there are still many unanswered questions concerning the release of such agents. The present program proposes an innovative, multidisciplinary approach to the investigation of cell communication processes at the molecular level. This proposal takes advantage of the combined expertise of two groups. The Center for Cell & Molecular Signaling (CCMS) will act to organize the biological expertise on the Emory campus while the Applied Sensors Laboratory (ASL) will act as the focal point on the Georgia Tech campus for development of the nanotechnology needed to study biological problems. CCMS and ASL already have established ongoing research programs and collaborative grants using nanotechnology to examine biologically active molecules in lung and renal cell systems. The interdisciplinary Program will focus on the application of integrated scanning nanoprobe sensing systems. Scanning probe microscopy techniques provide powerful means for obtaining chemical, topographical and optical information with high spatial resolution. Each technique -atomic force microscopy (AFM), scanning near field optical microscopy (SNOM) and scanning electrochemical microscopy (SECM) - is designed to provide a specific kind of biological data. SECM provides information on the activity of biological molecules at cell surfaces. Proof of concept experiments have already established the utility of such methods to measure paracrine agents like ATP and reactive oxygen species at cell surfaces with high temporal and spatial resolution, information required for in situ investigations of complex biological systems. This knowledge may lead to better understanding and new strategies for treatment of disorders specifically related to cell communication crocesses like diabetes, cystic fibrosis in the lung, and polycystic kidney disease.